This proposal seeks to examine, in animals and in humans, various suspected factors that interfere with the effects of the homotypical gonadal steroid hormones, i.e., estrogens in females, testosterone in males, upon central adrenergic functioning. Estrogens in females and testosterone in males normally inhibit the enzyme monoamine oxidase (MAO) thereby facilitating central adrenergic functioning. This effect appears to be diminished in depressed patients. Factors that could be responsible for this diminished effect are 1) excessive binding of the steroid hormones by blood protein molecules; and 2) excessive levels of antagonistic heterotypical gonadal hormones, i.e., testosterone in females, estrogens in males. This proposal would study these possibilities in humans and animals by examining blood levels of total and free estradiol and total and free testosterone and the metabolic clearance and production rates of these hormones in depressed an non- depressed men and women. Studies in rats will investigate the effect of varying doses of testosterone in female rats and estrogens in male rats on brain MAO activity and behavioral measures of CNS adrenergic functioning (wheel running). In addition the effects of chronic stress (electric shocks) upon blood levels of testosterone and estradiol and brain MAO activity in male and female rats will be studied.